The proposed 300 MHz NMR upgrade is needed to provide state-of-the-art 300 MHz NMR support for NIH sponsored research in the synthesis of natural and unnatural products and the bioorganic studies conducted in the laboratories of the major user group (Paul A. Grieco, William R. Roush, Theodore S. Widlanski, and David R. Williams). Among the synthetic organic and bioorganic research problems that the major user group will investigate are syntheses of rationally designed cysteine protease inhibitors and oligosaccharide-based binding agents (Roush); syntheses of complex antitumor compounds, remote hydroxylation of steroids and fundamental studies of medium effects on organic reactions (Grieco); synthesis and study of phosphatase inactivators and sulfonyl-containing oligonucleotides (Widlanski); and synthesis of macrolide antibiotics and novel marine natural products (Williams). Among the minor user group the instrument will be used for research in the discovery and development of new organic reactions and reactive intermediates (Jack K. Crandall), studies of the stereochemistry of thermal 1 ,3-sigmatropic shifts (Joseph J. Gajewski), and for research on the synthesis of supramolecular assembiles and the development of an experimentally determined scale functional group interaction energies (Mark D. Hollingsworth).